TMIHCV

Microfabrication-Based Rational Design of Transcriptional-Metabolic Intervention for the Treatment of Hepatitis C Virus (HCV) Infection

Coordinatore	THE HEBREW UNIVERSITY OF JERUSALEM.    more Spiacenti, non ci sono informazioni su questo coordinatore. Contattare Fabio per maggiori infomrazioni, grazie.
Nazionalità Coordinatore	Israel [IL]
Totale costo	1˙994˙395 €
EC contributo	1˙994˙395 €
Programma	FP7-IDEAS-ERC Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	ERC-2009-StG
Funding Scheme	ERC-SG
Anno di inizio	2010
Periodo (anno-mese-giorno)	2010-04-01   -   2015-03-31

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	THE HEBREW UNIVERSITY OF JERUSALEM.  Organization address address: GIVAT RAM CAMPUS city: JERUSALEM postcode: 91904 contact info Titolo: Dr. Nome: Yaakov Cognome: Nahmias Telefono: -9353862 Fax: -	IL (JERUSALEM)	hostInstitution	1˙994˙395.00
2	THE HEBREW UNIVERSITY OF JERUSALEM.  Organization address address: GIVAT RAM CAMPUS city: JERUSALEM postcode: 91904 contact info Titolo: Ms. Nome: Hani Cognome: Ben-Yehuda Telefono: +972 2 6586676 Fax: +972 2 6513205	IL (JERUSALEM)	hostInstitution	1˙994˙395.00

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 Obiettivo del progetto (Objective)

Hepatitis C Virus (HCV) infection affects over 3% of the world population and is the leading cause of chronic liver disease worldwide. Current treatments are effective in only 50% of the cases and associated with significant side effects. Therefore, there is a pressing need for the development of alternative treatments. Recently, our group and others demonstrated that the HCV lifecycle is critically dependent on host lipid metabolism. In this context, we demonstrated that the grapefruit flavonoid naringenin blocks HCV production through PPAR± and LXR±, transcriptional regulators of hepatic lipid metabolism. While these results are promising, our ability to rationally control metabolic pathways in infected cells is limited due to an incomplete understanding of the regulation of hepatic metabolism by its underlying transcriptional network. This project aims to develop a comprehensive model of hepatic metabolism by integrating metabolic fluxes with transcriptional regulation enabling the rational design of transcriptional-interventions which will minimize HCV replication and release. Our approach is to develop two microfabricated platforms that will enable high-throughput data acquisition and a human-relevant screening. One component is the Transcriptional Activity Array (TAA), a microdevice for the high-throughput temporal acquisition of transcriptional activity data. The second is the Portal Circulation Platform (PCP) which integrates intestinal absorption module with a liver metabolism compartment enabling the high-throughput human-relevant screening of treatments as a substitute to animal experiments. This work will lead to the development of novel drug combinations for the treatment of HCV infection and impact the treatment of diabetes, obesity, and dyslipidemia.